ArticleThe Journal of biological chemistry2012
Identification of membrane-bound variant of metalloendopeptidase neurolysin (EC 3.4.24.16) as the non-angiotensin type 1 (non-AT1), non-AT2 angiotensin binding site.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Discovery of a pyridine-piperazine-based small molecule that enhances the activity of peptidase neurolysin.The Journal of pharmacology and experimental therapeutics · 2026Article
- Discovery of the Next Generation of Non-peptidomimetic Neurolysin Activators with High Blood-Brain Barrier Permeability: a Pharmacokinetics Study in Healthy and Stroke Animals.Pharmaceutical research · 2023Article
- DNA methylation and 28-year cardiovascular disease risk in type 1 diabetes: the Epidemiology of Diabetes Complications (EDC) cohort study.Clinical epigenetics · 2023Article
- Small molecule neurolysin activators, potential multi-mechanism agents for ischemic stroke therapy.Expert opinion on therapeutic targets · 2022Article
- Identification and Characterization of Two Structurally Related Dipeptides that Enhance Catalytic Efficiency of Neurolysin.The Journal of pharmacology and experimental therapeutics · 2021Article
- Delayed atomoxetine or fluoxetine treatment coupled with limited voluntary running promotes motor recovery in mice after ischemic stroke.Neural regeneration research · 2021Article
- Delayed Exercise-induced Upregulation of Angiogenic Proteins and Recovery of Motor Function after Photothrombotic Stroke in Mice.Neuroscience · 2021Article
- Between two storms, vasoactive peptides or bradykinin underlie severity of COVID-19?Physiological reports · 2021Review
- Neurolysin substrates bradykinin, neurotensin and substance P enhance brain microvascular permeability in a human in vitro model.Journal of neuroendocrinology · 2021Article
- Investigation of Receptor Heteromers Using NanoBRET Ligand Binding.International journal of molecular sciences · 2021Article
- The role of peptidase neurolysin in neuroprotection and neural repair after stroke.Neural regeneration research · 2021Article
- Alterations in Gene Expression of Renin-Angiotensin System Components and Related Proteins in Colorectal Cancer.Journal of the renin-angiotensin-aldosterone system : JRAAS · 2021Article
- Peptidase neurolysin functions to preserve the brain after ischemic stroke in male mice.Journal of neurochemistry · 2020Article
- Peptidase neurolysin is an endogenous cerebroprotective mechanism in acute neurodegenerative disorders.Medical hypotheses · 2019Article
- Neurolysin: From Initial Detection to Latest Advances.Neurochemical research · 2018Review
- A Group of Weakly Bound to Neurons Extracellular Metallopeptidases (NEMPs).Neurochemical research · 2016Article
- Rational drug design and synthesis of molecules targeting the angiotensin II type 1 and type 2 receptors.Molecules (Basel, Switzerland) · 2015Review
- Electroosmotic perfusion of tissue: sampling the extracellular space and quantitative assessment of membrane-bound enzyme activity in organotypic hippocampal slice cultures.Analytical and bioanalytical chemistry · 2014Review
- The impact of age-related dysregulation of the angiotensin system on mitochondrial redox balance.Frontiers in physiology · 2014Review
- Distribution of non-AT1, non-AT2 binding of 125I-sarcosine1, isoleucine8 angiotensin II in neurolysin knockout mouse brains.PloS one · 2014Article
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Authors and funding
8 authors at 6 institutions in 3 countries.
Funding
Abstract
Recently, we discovered a novel non-angiotensin type 1 (non-AT1), non-AT2 angiotensin binding site in rodent and human brain membranes, which is distinctly different from angiotensin receptors and key proteases processing angiotensins. It is hypothesized to be a new member of the renin-angiotensin system. This study was designed to isolate and identify this novel angiotensin binding site. An angiotensin analog, photoaffinity probe 125I-SBpa-Ang II, was used to specifically label the non-AT1, non-AT2 angiotensin binding site in mouse forebrain membranes, followed by a two-step purification procedure based on the molecular size and isoelectric point of the photoradiolabeled binding protein. Purified samples were subjected to two-dimensional gel electrophoresis followed by mass spectrometry identification of proteins in the two-dimensional gel sections containing radioactivity. LC-MS/MS analysis revealed eight protein candidates, of which the four most abundant were immunoprecipitated after photoradiolabeling. Immunoprecipitation studies indicated that the angiotensin binding site might be the membrane-bound variant of metalloendopeptidase neurolysin (EC 3.4.24.16). To verify these observations, radioligand binding and photoradiolabeling experiments were conducted in membrane preparations of HEK293 cells overexpressing mouse neurolysin or thimet oligopeptidase (EC 3.4.24.15), a closely related metalloendopeptidase of the same family. These experiments also identified neurolysin as the non-AT1, non-AT2 angiotensin binding site. Finally, brain membranes of mice lacking neurolysin were nearly devoid of the non-AT1, non-AT2 angiotensin binding site, further establishing membrane-bound neurolysin as the binding site. Future studies will focus on the functional significance of this highly specific, high affinity interaction between neurolysin and angiotensins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.